Background: Patients with gastroenteropancreatic neuroendocrine carcinoma (NEC) have a poor prognosis. Platinum-based combination chemotherapy is commonly used as first-line treatment; however, because studies on salvage chemotherapy are limited, its role remains unknown. This study aimed to analyze the efficacy and safety of amrubicin monotherapy in patients with platinum-refractory gastroenteropancreatic NEC. Methods: Among 22 patients with advanced gastroenteropancreatic NEC, 10 received amrubicin monotherapy between September 2006 and May 2014 after failure of platinum-based chemotherapy. The efficacy and toxicity of the treatment were analyzed retrospectively. Results: Eight males and two females ((median age, 67 years (range, 52–78)) received platinum-based chemotherapy, including cisplatin plus irinotecan (n = 7, 70%), cisplatin plus etoposide (n = 2, 20%), and carboplatin plus etoposide (n = 1, 10%) before amrubicin therapy. A total of 30 cycles of amrubicin was administered in 10 patients, with a median number of cycles per patients was 2.5 (range, 1-7). Median progression-free survival (PFS) and overall survival after amrubicin therapy were 2.6 and 5.0 months, respectively. Two patients had partial response (20% response rate), and their PFS were 6.2 months and 6.3 months, respectively. Two patients with partial response had characteristics of NEC with a high Ki-67 index (99% and 89%, respectively) and had received cisplatin and irinotecan as first-line treatment. Grade 3–4 neutropenia and anemia were observed in four (40%) and five (50%) patients, and they were manageable in all cases by careful monitoring of myelosuppression and appropriate dose reduction of amrubicin. Conclusions: Amrubicin monotherapy appears to be potentially active and well-tolerated for platinum-refractory gastroenteropancreatic NEC.